Percutaneous Aortic Valve Replacement: A Chance for the Untreatable?
While percutaneous aortic valve replacements have been performed for more than six years in Europe, the option is not available to U.S. patients with severe aortic stenosis (AS) who are not surgical candidates, except for the select few enrolled in the Edwards Lifesciences PARTNER trial. With Medtronic applying for an FDA investigational device exemption (IDE), and a few other players emerging in Europe, the market seems explosive, but many clinical, ethical and financial questions need to be addressed before this therapy becomes a standard part of clinical practicein the U.S.

Where are we now?

Patients with severe symptomatic AS who are not operative candidates have an “extremely poor” prognosis, with survival rates as low as 50 percent at two years and 20 percent at five years after symptom onset (Heart 2000; 84;211-218). After the development of left ventricular failure, life expectancy is slightly greater than one year.

There remain no medical therapy options for the disease state. And along with the high risk of mortality, the “mode of death is horrible,” says Martin B. Leon, MD, an associate director of the Center for Interventional Vascular Therapy at New York Presbyterian Hospital/Columbia University Medical Center in New York City. “The patients often have recurrent rehospitalization, congestive heart failure, chest pain, fainting spells—it is a terrible way for a patient to die,” he adds.

Despite these concerns, many patients still are not referred for surgical treatment—which is the only approved treatment in the U.S. Only about 45 percent of patients with AS are referred for surgical aortic valve replacement (AVR) (Eur Heart J 2003;24:1231–1243). And, there remains a subset of patients who are not surgical candidates.

“Higher risk, elderly [older than 75 years] patients with severe AS have been widely undertreated,” says Eberhard Grube, MD, director of the department of cardiology at Heart-Center Siegburg in Germany, who has been utilizing the CoreValve transcatheter device in Europe for several years.

Yet, the newer transcatheter approach has arisen as a viable clinical option for these patients who are considered inoperable. In Europe, Medtronic’s CoreValve and the Edwards’ Sapien valve have regulatory approval. Meanwhile, two second-generation devices with smaller sheath sizes from Direct Flow Medical and Sadra Lotus are currently undergoing European trials. In the U.S., Edwards was granted an IDE for the ongoing PARTNER trial, and Medtronic has applied for an IDE from the FDA.

Peter C. Block, MD, director of clinical trials, department of cardiology at Emory University Hospital in Atlanta, acknowledges that the U.S. approach to AVR is more cautious than the European approach. “The problem with European data is that follow up has been historically difficult because of patient mobility. The FDA will want longer term results, before it approves this therapy,” he explains. Also, PARTNER is the first randomized, controlled trial to assess percutaneous AVR.

However, the specialty is exploding as it presents a novel way for physicians to treat an ailing—previously untreatable—population. Leon, who is the interventional principal investigator in PARTNER, explains that the field is in a “rapid period of data accumulation,” adding that the Edwards device was featured in approximately 80 peer-reviewed journals in 2009.

One of the reasons for the sudden popularity in percutaneous AVR is due to the positive outcomes. “Even with a conservative estimate, 10 lives per 100 can be saved per year,” says Jeffrey J. Popma, MD, director of innovations in interventional cardiology at Beth Israel Deaconess Medical Center in Boston. “Also, all the data thus far show that there are marked functional improvements in patients undergoing percutaneous AVR. A patient who would typically be consuming hospital services due to recurrent congestive heart failure now has Class I or Class II symptoms, and an improved quality of life.”

In fact, the European registry data show procedural success rates of 98 percent, a cardiac death rate of 9 percent and an overall one-year survival rate of 70 percent, Grube reports.

Which patients?

“Patients currently selected for percutaneous treatment are generally elderly with important associated diseases and have a finite lifespan,” Popma notes. “In contrast, the average 80-year-old without severe aortic stenosis can now expect, on average, another 8.8 years, compared with a near 40 percent one-year mortality rate in an inoperable patient with severe AS. AVR generally places patients back on their age-matched mortality curves.

“All these patients are sick and tend to have multiple co-morbidities, which can kill them,” says Block. As a result, he questions whether performing percutaneous AVR will be able to increase overall survival rates enough to obtain FDA approval.

“Also, CMS may mandate that it will not reimburse any patients that fall outside the very strict limits of the trials, even though that’s contradictory to history,” Block says. This cautionary approach may transfer to the physicians. “Historically, cardiologists have always taken the right to perform off-label procedures for the grey zone patient. I’m less certain that this path will be replicated with aortic valves,” he says.

While some physicians may whisper about trying this therapy in younger patients, Popma and Leon stress that surgical AVR remains a successful therapy for those patients who can undergo the procedure. “First, we need to establish whether we should be treating this higher risk subset percutaneously, then we’ll start to assess the lower risk subsets,” Popma says.

Leon says that the high-risk inoperable patients are the correct population in whom to start replacing aortic valves percutaneously. “We are very conscious of risk-creep,” which he defines as a broadening or expanding of indications in clinical practice, but thinks it is “unlikely” to happen for these patients.

While European physicians are sticking to the current protocols, Grube suggests if the long-term results prove safe and efficacious in the higher risk group, there is “no reason—and no doubt—that this will expand into the younger population with lesser risk of morbidity and mortality.”

One of the limitations to percutaneous AVR is peripheral arterial disease, which is common in the elderly. Therefore, the transapical approach is used with the Edwards device. “Transapical patients, by the fact that they have peripheral vascular disease, are higher risk patients, and therefore, have a higher mortality rate in the multiple registries from Europe,” says Block. In Europe, the CoreValve device can be introduced through the subclavian artery or direct aortic arch to gain access to the aorta.

Teamwork needed: Bridge to new profession?

The team approach will be necessary in the clinical setting for optimal care, explains Leon, because of all the considerations, including screening patients, access issues and complications. “It requires a team with both surgical and interventional skills,” he says. “We are entering an era now that not just valve therapy, but also coronary therapies require more of a team approach to decide which patients to treat with which therapy.”

At Emory, which is participating in the PARTNER trial, investigators are performing these procedures collegially, with each patient being presided over by two surgeons and two interventionalists, plus an echocardiographer and an anesthetist on standby.

“In the future, it may not make a lot of sense to have so much staff present, but it is not a procedure that can be performed solely by an interventionalist or solely by a cardiac surgeon,” says Block.

Popma adds that “surgeons and vascular surgeons may need to acquire angiographic imaging skills in an integrated surgical environment,” and if the procedure does get approved in the U.S., simulation training will be integral.

This new approach also may require surgeons to undergo a “fair amount of training” to acquire “reasonable catheter skills that allow them to perform portions of the procedure,” Leon speculates. “It’s naïve to think this should be in the interventionalist’s domain, as surgeons understand much more about valvular heart disease than interventionalists,” he says.

“We have continued to observe a significant learning curve,” Leon says. “If you’re not performing a requisite volume, your skills tend to degrade fairly quickly.”

If the therapy becomes available in the U.S., Block predicts that there will be a number of centers that will be asked to have proctors come for at least five or more cases. “This will be critically important, because this is not easy, and it can be helpful to have someone aide in the progression of the procedure,” he says.

However, Grube explains, in Europe, once an interventionalist gains a certain amount of experience, a surgeon is still present, but more as back up. However, he concurs that operator volume is directly correlated with procedural success. “This technology should be limited to high-volume, experienced centers with a team approach,” Grube notes.

What does this mean for providers?

In the U.S. provider setting, this team approach may require both an ideological and structural shift.

There are many economic and strategic considerations before a provider extends beyond a cardiovascular center to include an integrated structural heart center, which would be required for facilities to properly undertake these procedures.

“Most hospitals don’t have a clear integration of their vascular programs, cardiovascular programs and surgical programs. Likewise, most cardiologists do not currently work side-by-side with their surgeons in a hybrid OR,” explains Popma.

Percutaneous AVR is best performed in a hybrid OR, either because of complex access concerns or the development of vascular complications, says Popma, who adds that the room needs to accommodate the potential for “opening the chest without transporting the patient.”

Building a hybrid OR could cost a facility $5 million, according to Popma, and the provider might not gets its return on investment through direct procedures, but instead through the ability to have this lab as a backup. Also, the hospital could gain revenue through being more competitive in its geographic market by being able to offer advanced structural therapy.

Beth Israel uses its new hybrid OR about 30 percent of time for the necessary cases, but that 30 percent “couldn’t be done anywhere else,” Popma says.

Another justification for a provider to foster a structural heart program could be the revenue generated through simply screening this population, as 30 to 60 percent of patients with severe AS have never seen a cardiologist or surgeon. “It is not just about building hospital revenue,” Popma explains, “but also about developing sophisticated tools and skill sets within a particular setting to offer care to patients who might not have been considered at all for AVR.”

The ethical question

Throughout the past year’s debate on healthcare reform, people have often discussed the benefit to risk/cost ratio, leading some to ask whether it is cost effective or even ethical to treat such a high-risk population with multiple co-morbidities.

“Whether or not we treat patients who are very sick and attempt to improve their health at a relatively high cost is a large area of consternation, and boils down to end-of-life controversies,” Block states.

“If the ongoing clinical trials continue to prove successful in this elderly population, we can’t really question the value of this therapy,” Popma says. “In terms of healthcare economics, major reductions in mortality and morbidity are expected. We spend a lot more money on other therapies, which may be less cost-effective than reducing mortality and hospitalization in this patient population.”

In questioning the economics of end-of-life therapy, Leon believes this could be asked of a multitude of other therapies. “The U.S. does not ration medical care,” Leon says. Anecdotally, he adds that even patients over the age of 90 being treated in PARTNER, “are amazingly robust and very mentally cognizant. It is dismissive and improper to say that just because someone is elderly, [elderly patients] shouldn’t be candidates for the most advanced therapies. He or she shouldn’t be denied advanced therapies that allow them to appreciate their final years.”

While the technique matures in Europe and the U.S. trips along behind, the technologies continue to progress, always begging the questions: Will it provide better treatment for our patients? Is it financially responsible for our practice?